tbuckley/cabot-search huggingface dataset:
Utilization of metastatic hormone sensitive prostate cancer (mHSPC) treatment in a community oncology practice setting.
Authors: Terri Conner, Sreevalsa Appukkuttan, Sheldon Kong, Jay Jhaveri, Gilbert Ko, Bashir Kalayeh, LiHong He, Robert Sean Hauser, Arturo Loaiza-Bonilla
Journal: Journal of Clinical Oncology (2023)

86 Background: Treatment options for mHSPC have continued to evolve. While androgen deprivation therapy (ADT) has been the backbone treatment, more recently early use of docetaxel and/or novel androgen receptor inhibitors (nARIs) has demonstrated improved clinical outcomes. This study assessed real-world treatment among mHSPC patients who received at least one line of therapy (LoT). Methods: A retrospective observational study utilizing de-identified health records from five Cancer Treatment Centers of America (CTCA) included patients with metastatic prostate cancer who were treated with ADT, docetaxel or nARIs at CTCA for 6+ months between 1/2015-3/2021. Treatment patterns were observed from first LoT to metastatic castration resistance, death, or lost-to-follow-up until 3/2022. LoT was defined as first to last date of active drug therapy, not including long-term hormone agonists. First LoT was defined as initial regimen with no new drugs added 30+ days after start date. Patient characteristics, proportion and duration of each LoT, and reasons for early discontinuation were gathered using structured data elements and chart abstraction. Results: The characteristics of the 523 patients in this study were as follows: mean (SD) age 62 (8) years, 60% white and 33% black, 53% with commercial insurance, 75% with ECOG 0-1, and 65% with bone metastasis at diagnosis. Median follow-up time was 2.9 years. The most common LoT 1 regimen was either ADT alone or ADT with first generation androgen receptor inhibitors (FGARI) (table below). 46% received a second and 15% received a third LoT. Mean (SD) duration of first and second active LoTs were 12 (11.8) and 10 (11.1) months, respectively. Among the 65% and 78% patients who discontinued therapy in LoT 1 and 2, respectively, the majority discontinued due to progression of disease (35% LoT 1 and 53% LoT 2) followed by patient choice (23% LoT 1 and 18% LoT 2). Conclusions: Despite recommendations from guidelines on early intensification of therapy in mHSPC, in this contemporary cohort we find that most patients received either ADT alone or ADT ± FGARI in LoT 1 while chemotherapy and nARIs were initiated predominantly in later lines. Most patients discontinued LoT 1 due to disease progression which may suggest undertreatment and need for improved outcomes. Further studies are needed to assess the factors associated with non-intensification of treatments. [Table: see text]
Whole-body diffusion-weighted magnetic resonance imaging to assess bone response in patients with hormone-sensitive metastatic prostate cancer randomly assigned to receive androgen deprivation + enzalutamide ± zoledronic acid.
Authors: Alberto Dalla Volta, Francesca Valcamonico, Andrea Zivi, Giuseppe Procopio, Pierangela Sepe, Gianluca Del Conte, Nunzia Di Meo, Silvia Foti, Stefania Zamboni, Caterina Messina, Eleonora Lucchini, Anna Rizzi, Marco Ravanelli, Michele Milella, Stefano Calza, Claudio Simeone, Roberto Maroldi, Davide Farina, Alfredo Berruti
Journal: Journal of Clinical Oncology (2023)

46 Background: Bone is frequently involved in metastatic hormone sensitive prostate cancer (mHSPC). Whole-body diffusion-weighted magnetic resonance imaging (WB-DW-MRI) is a promising imaging technique for the assessment of bone response in prostate cancer. It is not known whether the addition of antiresorptive agents can improve disease response in bone in mHSPC patients undergoing next generation hormonal agents. Methods: In this multicenter phase II study patients with de novo or relapsed mHSPC and bone metastases at bone scan were randomly allocated with a 1:1 ratio to receive either androgen deprivation therapy (ADT) plus Enzalutamide (E arm) or the same combination with the addition of Zoledronic Acid (EZ arm). The study was designed to observe a significant increase in bone response rate in the experimental arm after 12 months of treatment, as assessed through WB-DW-MRI. WB-DW-MRI was performed centrally at baseline and after 6 and 12 months and images were evaluated by the same radiologist. Results: From February 2018 to June 2021, 126 mHSPC patients were randomized, 64 in EZ arm and 62 in E arm. A total of 111 patients, 54 from E arm and 57 from EZ arm, were eligible for WB-DW-MRI assessment (15 patients were excluded because of the absence of bone target lesions at MRI or specific contraindications to MRI). Bone response at 6 months was observed in 41 patients (76%) in E arm and 41 patients (72%) in EZ arm; the corresponding bone response at 12 months were 44 (82%) and 44 (77%), respectively (OR 0.77; 95%IC 0.30-1.93; p = 0.6). Complete response was the best overall bone response after 12 months in 9 patients (17%) from E arm and in 11 patients (19%) from EZ arm. In the same period, treatment was interrupted due to disease progression in 7 (13%) and 7 (12%) patients in E and EZ arm, respectively. Conclusions: The addition of Zoledronic Acid to Enzalutamide and ADT did not improve bone disease response in patients with mHSPC. WB-DW-MRI was able to detect bone responses in a great proportion of patients. Clinical trial information: NCT03336983 .
Comparative analysis of contemporary and past PSMA PET/CT results for recurrent prostate cancer in a high-volume Brazilian center.
Authors: Dr. Paulo Sergio Lages, Luciano Monteiro do Prado Junior, Leonardo Fonseca Monteiro do Prado, Bruno Carvalho Oliveira, Renato Ramos Barra, Michelle Silva Barbosa, Daniel Vargas Pivato de Almeida
Journal: Journal of Clinical Oncology (2023)

51 Background: PSMA PET/CT scan ( 68 Ga-PSMA PET/CT) has emerged as a highly accurate tool when assessing disease staging both for newly diagnosed localized high-risk prostate cancer and for recurrent disease, with treatment plan modification in up to two-thirds of patients. PSMA PET/CT is commercially available in Brazil since last decade and growing experience with this test has led to a more accurate analysis of the results over the years. Methods: We retrospectively reviewed the PSMA PET/CT scans results of patients undergoing the exam in all disease stages in a single institution in Brasilia, Brazil, between October 2015 and July 2022 and analyzed the results correlated with clinicopathological information (when available) in two separated timeframes for those in the recurrent disease setting. Results: Overall, more than 2,500 PSMA PET-CT scans were performed since October 2015. Between 2015 and 2019, 351 exams were performed, of which 303 in the setting of recurrent disease, while 297 tests were executed between 2021 and 2022, with 283 of them being done in the recurrent disease setting. Any clinicopathological information was available for 648 patients, of whom 586 underwent the test in the setting of recurrent disease following treatment of primary disease. Conclusions: There was a similar positivity rate among the clinicopathological characteristics analyzed in an indirect comparison of the two timeframes. It is remarkable the increased positivity rate among patients with lower levels of PSA in the contemporary dataset, which may reflect the learning curve of this image method. Among patients selected by Gleason grade, no definitive information can be extracted given the distinct PSA levels between patients in the two selected timeframes. [Table: see text]
A phase 1, open-label trial to evaluate feasibility and safety of intramural injection of belzupacap sarotalocan (AU-011) in non-muscle–invasive bladder cancer (NMIBC).
Authors: Seth P. Lerner, Trinity Bivalacqua, Isaac Yi Kim, Carrie Murray, Cadmus Collins Rich, Piyush K. Agarwal, Neal D. Shore
Journal: Journal of Clinical Oncology (2023)

TPS596 Background: A high unmet medical need exists for new therapies in NMIBC to reduce common risks of recurrence, progression and, ultimately, cystectomy. Belzupacap sarotalocan, a novel investigational virus-like drug conjugate (VDC), has a dual mechanism of action designed to provide 1) selective binding to malignant cells, causing acute necrosis upon light activation, and 2) long-term anti-tumor immunity as demonstrated in pre-clinical models. This Phase 1 trial is designed to evaluate the feasibility and safety of intramural injection with or without intratumoral injection of belzupacap sarotalocan for treatment of NMIBC. The hypothesis is that after near infrared light activation, targeted distribution of belzupacap sarotalocan at high concentrations at the tumor base could necrose the tumor where it is most likely to be invasive. In turn, the tumor targeted pro-immunogenic cell death could potentially lead to an anti-tumor immune response preventing the risk for recurrence, progression and metastasis. Methods: This is an actively enrolling “window of opportunity” trial (NCT05483868) in low, medium or high risk NMIBC subjects scheduled to undergo TURBT or cystectomy per standard of care. A pre-treatment biopsy will be performed in up to 23 adult subjects enrolled in 4 cohorts, who will be given belzupacap sarotalocan +/- laser as shown in the table. The primary endpoint is incidence and severity of treatment-related adverse events, serious adverse events regardless of attribution, and incidence of dose-limiting toxicities. Each cohort will have a safety review for the injection procedure and laser (as needed), after 3 subjects have been treated and followed for 28 days. Secondary endpoints are based on histopathology and include assessment of local biodistribution of belzupacap sarotalocan measured via immunohistochemical staining, tumor necrosis, and evidence of an immune response via comparison of pre-treatment biopsy to TURBT/cystectomy samples after treatment. Statistical analysis plan includes descriptive statistics for the above endpoints. Clinical trial information: NCT05483868 . [Table: see text]
Polo-like kinase-1 as a potential prognostic marker of prostate cancer utilizing ORIEN data.
Authors: Snigdha Nutalapati, Chi Wang, Alice X Liu, Zhuwei Zhang, Howard Colman, Elaine T. Lam, John D. Carpten, Eric A. Singer, Nabil Adra, Michael Edward Devitt, Jad Chahoud, Abhishek Tripathi, Kelly Lynn Stratton, Zin Myint
Journal: Journal of Clinical Oncology (2023)

384 Background: Polo-Like Kinase-1(PLK1) is one of the key regulators in G2/M cell cycle. Preclinical studies have shown that PLK1 might be involved in treatment resistance in prostate cancer (PCa). PLK1 overexpression by immunohistochemistry is associated with higher Gleason grade and thus PLK1 could play a role in PCa tumorigenesis. In this study, we utilized a different methodology by using RNA-seq PLK1 expression and correlated with clinical outcomes. Methods: Patients with all stages of prostate adenocarcinoma diagnosed between 2014 and 2020 from nine participating members of the Oncology Research Information Exchange Network (ORIEN) were included in the study. Tumor RNA-seq was analyzed for PLK1 expression and associated with clinical data obtained from ORIEN AVATAR. PLK1 expression was stratified into high expression (defined as ≥75 th percentile of PLK1 mRNA expression) vs. low expression (≤75 th percentile). Univariate and multivariate Cox proportional hazard model were used to compare overall survival between patients with low vs high PLK1 expression adjusting for age, race, PSA and stage. Results: A total of 452 tumors were evaluated for PLK1 expression. Of those, 241 (53.3%) had high PLK1 and 211 (46.7%) had low PLK1 expression. Median age at diagnosis for high and low PLK1 expression was 64.5 and 63.2 years respectively. The majority of patients were Caucasian in both groups. In high PLK1 group, 93 (65%) had localized high risk/very high risk disease, 27 (19%) had localized intermediate risk, 20 (14%) had metastatic vs. 97 (63%), 38 (25%) and 18(12%) respectively in low PLK1 group. Gleason ≥ 8 and PSA &lt;20 were seen slightly more in high PLK1 compared to low PLK1; 40% vs 33% and 96% vs.94% respectively. The median follow-up time was 2.74 years in low PLK1 group and 2.71 years in high PLK1 group. There was no difference between PLK1 low vs. high expression for age, race, stage, PSA and Gleason grade. There was no difference in overall survival between low PLK1 and high PLK1 expression by univariate analysis (p=0.86; HR 1.09) or after adjusting for multivariate analysis (p=0.85; HR 1.12). Conclusions: In our study, we did not find RNA-seq PLK1 expression as a potential prognostic marker for prostate cancer. There was no survival difference between low PLK1 vs. high PLK1 expression.
Proposal for reclassification of upstaged T1 and T2 and pathological T3 RCC based on improved alignment of survival analyses.
Authors: Margaret Meagher, Clara Cerrato, Dhruv Puri, Franklin Liu, Aastha Shah, Saeed Ghassemzadeh, Sohail Dhanji, Luke Wang, Dattatraya H Patil, Kazutaka Saito, Yosuke Yasuda, Ryan Nasseri, Yasuhisa Fujii, Viraj A. Master, Ithaar H Derweesh
Journal: Journal of Clinical Oncology (2023)

732 Background: Patients with pathologically upstaged tumors have worse survival outcomes than their non-upstaged matched counterparts. However, we do know that original clinical tumor staging does still predict outcomes. We sought to examine if pathologic upstaging incrementally may more rationally stratify cancer specific survival outcomes. Methods: Multi-institutional (Emory, TMDU, UCSD) retrospective analysis of patients with renal cell carcinoma who underwent partial or radical nephrectomy between 1998-2020. Patients were divided into cT1 upstaged to pT3 (cT1/pT3), cT2 non-upstaged (cT2/pT2), cT2 upstaged to pT3 (cT2/pT3), and cT3 non-upstaged (cT3/pT3). Patients were analyzed for demographics, clinical parameters, and post-surgical outcomes. Primary outcome was cancer specific mortality (CSM). Secondary outcomes were all cause mortality and recurrence free survival. Cox regression was utilized to analyze factors associated with outcomes. Kaplan Meier analysis (KMA) was performed to analyze 5-year cancer specific survival. ROC analysis was utilized to compare predictive value of AJCC 8 th edition TNM staging vs proposed staging. Results: 1093 patients were analyzed (283 cT1/pT3, 237 cT2/pT2, 244 cT2/pT3, and 329 cT3/pT3). Median follow-up was 25.9 months. Cox regression demonstrated that cT2/pT3 (HR 2.7, p&lt;0.001 vs. cT1/pT3 [referent]) and cT3/pT3 (HR 2.6, p&lt;0.001 vs. cT1/pT3 [referent]) were significantly associated with worsened cancer specific mortality, while cT1/pT3 (HR 0.4, p&lt;0.001 vs. cT3/pT3 [referent]) and cT2/pT2 (HR 0.4, p&lt;0.001 vs. cT3/pT3 [referent]) were associated with improved cancer specific mortality. Based on this, we proposed to realign cT1/pT3 with cT2/pT2 and cT2/pT3 with cT3/pT3. KMA revealed significant differences in 5-year cancer specific survival (cT1/pT3 82%, cT2/pT2 81%, cT2/pT3 67%, and cT3/pT3 60%, p&lt;0.001). There were significant differences in 5-year overall survival (cT1/pT3 63%, cT2/pT2 67%, cT2/pT3 49%, and cT3/pT3 49%, p&lt;0.001), and 5-year recurrence free survival (cT1/pT3 80%, cT2/pT2 83%, cT2/pT3 70%, and cT3/pT3 59%, p&lt;0.001) on KMA. ROC analysis revealed an AUC of 0.529 for CSM and AUC of 0.502 for ACM using the current AJCC 8 th edition TNM staging. ROC analysis revealed an AUC of 0.597 for CSM and AUC of 0.545 for our new proposal. Conclusions: Our analysis suggests that cT1 tumors pathologically upstaged to pT3 behave more similarly to pT2 tumors. Further delineation of pathologically upstaged tumors may more rationally stratify cancer specific survival outcomes to guide patient counseling and clinical decision making.
Prediction of significant prostate cancer in equivocal MRI lesions: A high-volume international multicenter study.
Authors: August Sigle, Angelika Borkowetz, Jost von Hardenberg, Martin Drerup, Kira Kornienko, Christian Gratzke, Samy Mahjoub
Journal: Journal of Clinical Oncology (2023)

311 Background: The decision of performing prostate biopsy in men with equivocal findings in prostate magnetic resonance imaging (MRI) is challenging as they have a low but still relevant risk of harboring significant prostate cancer (sPC). Objective: To identify clinical predictors of sPC in men with equivocal findings in prostate MRI. Secondly, we aimed to analyze the hypothetical effect of incorporating prostate-specific antigen density (PSAD) into biopsy decision. Methods: We analysed a retrospective multinational cohort from 10 academic centers comprising 1476 men who underwent combined prostate biopsy (MRI-targeted plus systematic) between 02/2012 – 04/2021 due to an equivocal lesion found in prostate MRI (Prostate Imaging Reporting and Data System 3). Primary outcome was the detection of sPC (ISUP ≥ 2) in combined biopsy. Regression analysis was performed to identify predictors for this outcome. Descriptive statistics were applied to evaluate the hypothetical effect of involving PSAD into biopsy decision. Results: 273/1476 (18.5%) men were diagnosed with sPC by combined biopsy. MRI-targeted biopsy diagnosed less sPC as compared to combined strategy: 183/1476 (12.4%) vs. 273/1476 (18.5%), p&lt;0.01. Regression analysis confirmed age (OR 1.10 [95% CI: 1.05 – 1.15]; p &lt; 0.001), prior negative biopsy (OR 0.46 [0.24 – 0.89]; p = 0.022) and PSAD (p&lt;0.001) as independent predictors for sPC. Applying a PSAD cut-off of 0.15 for biopsy decision, 817/1398 (58.4%) of the biopsy procedures would have been avoided at the cost of missing sPC in 91 (6.5%) men. Limitations were the retrospective design, heterogeneity of the study cohort due to the long inclusion period and a missing central revision of MRI. Conclusions: Age, previous biopsy status and PSAD were found independent predictors of sPC in men with equivocal prostate MRI. Implementation of PSAD into biopsy decision can avoid a large proportion of unnecessary biopsies. Clinical parameters such as PSAD need validation in a prospective setting.
Frailty and overall survival in metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide.
Authors: Ekamjit Singh Deol, Suhong Luo, Kristen Marie Sanfilippo, Seth A Eisen, Martin W. Schoen
Journal: Journal of Clinical Oncology (2023)

71 Background: Abiraterone (ABI) and Enzalutamide (ENZ) are both treatment options for metastatic castration-resistant prostate cancer (mCRPC). However, both drugs have differing pharmacodynamics, so patient factors may selectively impact drug efficacy. Age-associated health deficits make older adults variably susceptible to disease under a syndrome termed frailty. The average age of initial prostate cancer diagnosis is age 66, and the average time to mCRPC progression is 11.7 years. Thus, frailty is an important patient factor to consider in mCRPC, and it may play a role in personalizing drug selection. Methods: Patients treated with ABI or ENZ for mCRPC from September 2014 to June 2017 were identified in the VA and followed until April 2020. Frailty was assessed using the VA frailty index, which looks at ICD-10, CPT, and HCPCS codes to assign a standardized frailty score between 0-1. Patients were categorized as frail if their VA-FI scores were &gt; 0.2. The primary outcome was overall survival (OS) between the ABI and ENZ treatment groups. Cox regression models included age, race, body mass index, PSA, and total Charlson Comorbidity Index (CCI). For frail patients, a propensity score-matched cohort was also created by matching age, race, CCI, and total VA-FI between ABI and ENZ treatment groups. Results: Of the 5,822 patients identified, 57% were initially treated with ABI and 43% with ENZ. The ABI group had a lower mean VA-FI score of 0.192 compared to the ENZ group of 0.203 (p=0.004). Frail patients were older: mean 74.9 years vs. 76.1 years for non-frail (p&lt;0.001). Frail patients had shorter survival than non-frail (18.5 vs. 26.6 months, p&lt;0.001). In multivariable models, frailty was associated with increased risk of death (aHR 1.32, 95% CI 1.23-1.42). Among non-frail patients (n=3508, 60.3%), there was no significant difference in OS between ABI and ENZ treatment. Among frail patients (n=2314, 39.7%), patients treated with ENZ had a 3.5 month greater median OS than ABI (20.7 vs. 17.2 months, p = 0.0003 by log-rank). In frail patients, ENZ was associated with reduced risk of death (aHR 0.85, 95% CI 0.78-0.94). In a propensity matched cohort of 2070 patients, the enzalutamide treatment group had a 3.2 months greater median OS in the enzalutamide group than the abiraterone group (24.1 months vs. 20.9 months, p &lt; 0.001). Conclusions: ENZ was associated with improved OS compared to ABI among frail veterans, but not among non-frail veterans. The improved survival remained significant in a propensity score-matched cohort and models including important covariates. Further assessment of the value of frailty in personalizing drug treatment is warranted to improve the care of older adults with advanced prostate cancer.
Real world rates of genetic referrals and germline testing in patients with prostate adenocarcinoma at an academic cancer center in southern New Jersey.
Authors: Christopher Ambrogi, Sahaj Desai, Randi Zukas Carhart, Jenia Jenab-Wolcott, Julia Chia-Ying Shih
Journal: Journal of Clinical Oncology (2023)

114 Background: Prostate adenocarcinoma is the second leading cause of cancer-related death in men in the United States. A major risk factor is family history, with prostate cancer in a first-degree relative effectively doubling a patient’s risk. However, relying on family history alone fails to identify many patients with clinically relevant cancer-related germline mutations, which can have important prognostic and therapeutic implications for patients and their families. In 2018, the NCCN recommended expanding the germline testing to include all men with high risk, very high risk, regional or metastatic prostate cancer. We sought to identify the rate of genetic testing within this patient population at the MD Anderson Cancer Center at Cooper University Hospital. Methods: The institution database was queried to identify patients with the ICD-10 diagnosis of prostate adenocarcinoma between 01-2019 and 12-2020; the inclusion criteria were age 18 years or older, biopsy-proven prostate adenocarcinoma, and qualification to receive germline genetic testing per NCCN guidelines. A total of 201 patients were screened and 97 cases were analyzed. Results: Of the 97 patients who qualified for genetic testing, 53 were referred to genetics (54.6%). 27 of the 53 patients who met with our genetics team underwent testing (50.9%). Of the 27 patients tested, nine patients (33.3%) were found to have clinically relevant cancer-related germline mutations with therapeutic implications for the patient and/or screening recommendations for the patient and their family members. Conclusions: Overall, the proportion of patients who qualified for and completed genetic testing was low at 27.8%. Of those who completed testing, the rate of detection of a significant germline mutation was high at 33.3%, indicating that a significant proportion of those untested may carry a genetic mutation of clinical importance. Based on these results, we developed an electronic Best Practice Alert that notifies providers if a patient qualifies for a genetic risk evaluation based on his prostate cancer risk. We implemented this system, with reported high utilization demonstrating feasibility of this tool. Preliminary data shows improved rates of referral among prostate cancer patients.